TMPRSS3 c.*287C>T
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.14%, mid)
Conditions
1
autosomal recessive nonsyndromic hearing loss 8
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -0.62, phastCons 0.003 |
| Non-coding constraint | Z 0.73 | 1 kb window · o/e 0.93 · regional · uncalibrated |
| Overall | ||
| CADD | 2.268 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.14%
Middle Eastern · 3/2,136 alleles
Filtering AF
0.0382%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0204%
Overall
0.0103%
60/582,744 alleles · rare
exomes 44/430,550 · genomes 16/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.14% | 712 |
| Remaining individualsnot grpmax-eligible | 0.0281% | 3,564 |
| South Asian | 0.0244% | 4,101 |
| Admixed American | 0.00863% | 11,590 |
| European (non-Finnish) | 0.00771% | 12,973 |
| African / African-American | 0.00736% | 13,590 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00513% | 19,504 |
| East Asian | 0.00402% | 24,866 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- TMPRSS3
- Coding
- c.*287C>T
- MANE Select
- NM_001256317
- dbSNP
- rs757369320
- Type
- single nucleotide variant
- Location
- chr21:42372475 (GRCh38)
- Gene constraint
- LOEUF 1.106 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.09
Similar variants
- TMPRSS3 c.1049-4G>A Likely pathogenic ★★ same condition
- TMPRSS3 c.206-2A>G Likely pathogenic ★★ same condition
- TMPRSS3 c.323-6G>A Pathogenic/Likely pathogenic ★★ same condition
- TMPRSS3 c.446+1G>T Likely pathogenic ★★ same condition
- TMPRSS3 c.573-1G>A Likely pathogenic ★★ same condition
- TMPRSS3 p.Ala138Glu Pathogenic/Likely pathogenic ★★ same condition
- TMPRSS3 p.Ala306Thr Pathogenic/Likely pathogenic ★★ same condition
- TMPRSS3 p.Ala306Val Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tmprss3-c-star-287c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown